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Frontiers in Immunology 2021In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral...
In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral cavity, oropharynx, esophagus, stomach and bowel. In this report, we describe an autopsy case of a COVID-19 patient who showed two undiagnosed ulcers at the level of the anterior and posterior walls of the hypopharynx. Molecular testing of viruses involved in pharyngeal ulcers demonstrated the presence of severe acute respiratory syndrome - coronavirus type 2 (SARS-CoV-2) RNA, together with herpes simplex virus 1 DNA. Histopathologic analysis demonstrated full-thickness lympho-monocytic infiltration (mainly composed of CD68-positive cells), with hemorrhagic foci and necrosis of both the mucosal layer and deep skeletal muscle fibers. Fibrin and platelet microthrombi were also found. Cytological signs of HSV-1 induced damage were not found. Cells expressing SARS-CoV-2 spike subunit 1 were immunohistochemically identified in the inflammatory infiltrations. Immunohistochemistry for HSV1 showed general negativity for inflammatory infiltration, although in the presence of some positive cells. Thus, histopathological, immunohistochemical and molecular findings supported a direct role by SARS-CoV-2 in producing local ulcerative damage, although a possible contributory role by HSV-1 reactivation cannot be excluded. From a clinical perspective, this autopsy report of two undiagnosed lesions put the question if ulcers along the GI tract could be more common (but frequently neglected) in COVID-19 patients.
Topics: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Autopsy; Blood Platelets; COVID-19; Gastrointestinal Tract; Herpesvirus 1, Human; Humans; Hypopharynx; Immunohistochemistry; Inflammation; Lymphocytes; Monocytes; Mucous Membrane; Muscle, Skeletal; Necrosis; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Thrombosis; Ulcer
PubMed: 34290701
DOI: 10.3389/fimmu.2021.676828 -
Immunity Aug 2021Lymphoid stromal cells (LSCs) are essential organizers of immune responses. We analyzed tonsillar tissue by combining flow cytometry, in situ imaging, RNA sequencing,...
Lymphoid stromal cells (LSCs) are essential organizers of immune responses. We analyzed tonsillar tissue by combining flow cytometry, in situ imaging, RNA sequencing, and functional assays, defining three distinct human LSC subsets. The integrin CD49a designated perivascular stromal cells exhibiting features of local committed LSC precursors and segregated cytokine and chemokine-producing fibroblastic reticular cells (FRCs) supporting B and T cell survival. The follicular dendritic cell transcriptional profile reflected active responses to B cell and non-B cell stimuli. We therefore examined the effect of B cell stimuli on LSCs in follicular lymphoma (FL). FL B cells interacted primarily with CD49a FRCs. Transcriptional analyses revealed LSC reprogramming in situ downstream of the cytokines tumor necrosis factor (TNF) and transforming growth factor β (TGF-β), including increased expression of the chemokines CCL19 and CCL21. Our findings define human LSC populations in healthy tissue and reveal bidirectional crosstalk between LSCs and malignant B cells that may present a targetable axis in lymphoma.
Topics: B-Lymphocytes; Cells, Cultured; Chemokine CCL19; Chemokine CCL21; Dendritic Cells; Humans; Integrin alpha1; Lymphoma, Follicular; Palatine Tonsil; Signal Transduction; Stromal Cells; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha
PubMed: 34166622
DOI: 10.1016/j.immuni.2021.05.019 -
Parasites & Vectors May 2021The liver fluke Fasciola gigantica secretes excretory-secretory proteins during infection to mediate its interaction with the host. In this study, we investigated the...
BACKGROUND
The liver fluke Fasciola gigantica secretes excretory-secretory proteins during infection to mediate its interaction with the host. In this study, we investigated the immunomodulatory effects of a recombinant tegumental calcium-binding EF-hand protein 4 of F. gigantica (rFg-CaBP4) on goat monocytes.
METHODS
The rFg-CaBP4 protein was induced and purified by affinity chromatography. The immunogenic reaction of rFg-CaBP4 against specific antibodies was detected through western blot analysis. The binding of rFg-CaBP4 on surface of goat monocytes was visualized by immunofluorescence assay. The localization of CaBP4 within adult fluke structure was detected by immunohistochemical analysis. The cytokine transcription levels in response to rFg-CaBP4 were examined using ABI 7500 real-time PCR system. The expression of the major histocompatibility complex (MHC) class-II molecule (MHC-II) in response to rFg-CaBP4 protein was analyzed using Flow cytometry.
RESULTS
The isopropyl-ß-D-thiogalactopyranoside-induced rFg-CaBP4 protein reacted with rat sera containing anti-rFg-CaBP4 polyclonal antibodies in a western blot analysis. The adhesion of rFg-CaBP4 to monocytes was visualized by immunofluorescence and laser scanning confocal microscopy. Immunohistochemical analysis localized native CaBP4 to the oral sucker, pharynx, genital pore, acetabulum and tegument of adult F. gigantica. Co-incubation of rFg-CaBP4 with concanavalin A-stimulated monocytes increased the transcription levels of interleukin (IL)-2, IL-4, interferon gamma and transforming growth factor-β. However, a reduction in the expression of IL-10 and no change in the expression of tumor necrosis factor-α were detected. Additionally, rFg-CaBP4-treated monocytes exhibited a marked increase in the expression of the major histocompatibility complex (MHC) class-II molecule (MHC-II) and a decrease in MHC-I expression, in a dose-dependent manner.
CONCLUSIONS
These findings provide additional evidence that calcium-binding EF-hand proteins play roles in host-parasite interaction. Further characterization of the immunomodulatory role of rFg-CaBP4 should expand our understanding of the strategies used by F. gigantica to evade the host immune responses.
Topics: Animals; Calcium-Binding Proteins; Cytokines; Fasciola; Fascioliasis; Goats; Immunomodulation; Monocytes; Recombinant Proteins
PubMed: 34022913
DOI: 10.1186/s13071-021-04784-5 -
Annals of Palliative Medicine Jul 2021Necrotizing fasciitis (NF) is a rare, fulminant, lethal soft-tissue infection result in fascial necrosis, it is rarer in the head and neck area. Infection caused by...
Necrotizing fasciitis (NF) is a rare, fulminant, lethal soft-tissue infection result in fascial necrosis, it is rarer in the head and neck area. Infection caused by Klebsiella oxytoca is much less common. Therefore, we reported a case of NF in the maxillofacial region, neck and upper mediastinum caused by Klebsiella oxytoca as the main cause recently treated in our department. The patient is a middle-aged male with a 10-year history of diabetes with unstable insulin control. The main symptoms were pain on left side with dysphagia and fever and the situation was getting worse. The patient had limited ability to have mouth open and had hyperemia, swelling on the left pharynx, maxillofacial area, and upper left neck and skin tenderness, and all symptoms were getting worse quick. The CT mainly found out that left oropharyngeal wall, parotid gland area, bilateral submaxilla, left neck, and superior mediastinum are swelling with gas. The blood test result: leukocytes count 16.64×109/L, neutrophils percentage 85.8%; C-Pr 320 mg/L; urinary routine: urine glucose (+++++), ketone bodies (+++++); fasting glucose metabolism: glucose 21.33 mmol/L, glycosylated albumin 47.67%. Three incisions of facial and neck were performed to drain pus. Result of bacteria culture: Klebsiella oxytoca and Streptococcus constellatus During treatment of DKA and reduce patient glucose level, we also treated patient with neck and trachea incisions to drain pus and cleaned daily wound area and used different antibiotics according to the bacteria culture and CT results. And finally, the patient was cured and discharged from hospital. This case of NF was very rare not only the bacteria in this case but also the pathological changes related (involving the mediastinum). The report of his diagnosis and treatment can provide experience for future treatments.
Topics: Fasciitis, Necrotizing; Humans; Klebsiella oxytoca; Male; Mediastinum; Middle Aged; Neck; Streptococcus constellatus
PubMed: 33977729
DOI: 10.21037/apm-20-2427 -
EBioMedicine May 2021Coronavirus-2 (SARS-CoV-2) infection causes an acute respiratory syndrome accompanied by multi-organ damage that implicates a prothrombotic state leading to widespread...
BACKGROUND
Coronavirus-2 (SARS-CoV-2) infection causes an acute respiratory syndrome accompanied by multi-organ damage that implicates a prothrombotic state leading to widespread microvascular clots. The causes of such coagulation abnormalities are unknown. The receptor tissue factor, also known as CD142, is often associated with cell-released extracellular vesicles (EV). In this study, we aimed to characterize surface antigens profile of circulating EV in COVID-19 patients and their potential implication as procoagulant agents.
METHODS
We analyzed serum-derived EV from 67 participants who underwent nasopharyngeal swabs molecular test for suspected SARS-CoV-2 infection (34 positives and 33 negatives) and from 16 healthy controls (HC), as referral. A sub-analysis was performed on subjects who developed pneumonia (n = 28). Serum-derived EV were characterized for their surface antigen profile and tested for their procoagulant activity. A validation experiment was performed pre-treating EV with anti-CD142 antibody or with recombinant FVIIa. Serum TNF-α levels were measured by ELISA.
FINDINGS
Profiling of EV antigens revealed a surface marker signature that defines circulating EV in COVID-19. A combination of seven surface molecules (CD49e, CD209, CD86, CD133/1, CD69, CD142, and CD20) clustered COVID (+) versus COVID (-) patients and HC. CD142 showed the highest discriminating performance at both multivariate models and ROC curve analysis. Noteworthy, we found that CD142 exposed onto surface of EV was biologically active. CD142 activity was higher in COVID (+) patients and correlated with TNF-α serum levels.
INTERPRETATION
In SARS-CoV-2 infection the systemic inflammatory response results in cell-release of substantial amounts of procoagulant EV that may act as clotting initiation agents, contributing to disease severity.
FUNDING
Cardiocentro Ticino Institute, Ente ospedaliero Cantonale, Lugano-Switzerland.
Topics: Adult; Aged; Aged, 80 and over; Antigens, Surface; Biomarkers; COVID-19; Case-Control Studies; Diagnosis, Differential; Extracellular Vesicles; Female; Humans; Male; Middle Aged; Nasopharynx; SARS-CoV-2; Switzerland; Thromboplastin; Thrombosis; Tumor Necrosis Factor-alpha
PubMed: 33971404
DOI: 10.1016/j.ebiom.2021.103369 -
PLoS Neglected Tropical Diseases Apr 2021Naja atra is a major venomous snake found in Taiwan. The bite of this snake causes extensive wound necrosis or necrotizing soft tissue infection. Conventional microbial...
An investigation of conventional microbial culture for the Naja atra bite wound, and the comparison between culture-based 16S Sanger sequencing and 16S metagenomics of the snake oropharyngeal bacterial microbiota.
Naja atra is a major venomous snake found in Taiwan. The bite of this snake causes extensive wound necrosis or necrotizing soft tissue infection. Conventional microbial culture-based techniques may fail to identify potential human pathogens and render antibiotics ineffective in the management of wound infection. Therefore, we evaluated 16S Sanger sequencing and next-generation sequencing (NGS) to identify bacterial species in the oropharynx of N. atra. Using conventional microbial culture methods and the VITEK 2 system, we isolated nine species from snakebite wounds. On the basis of the 16S Sanger sequencing of bacterial clones from agar plates, we identified 18 bacterial species in the oropharynx of N. atra, including Morganella morganii, Proteus vulgaris, and Proteus mirabilis, which were also present in the infected bite wound. Using NGS of 16S metagenomics, we uncovered more than 286 bacterial species in the oropharynx of N. atra. In addition, the bacterial species identified using 16S Sanger sequencing accounted for only 2% of those identified through NGS of 16S metagenomics. The bacterial microbiota of the oropharynx of N. atra were modeled better using NGS of 16S metagenomics compared to microbial culture-based techniques. Stenotrophomonas maltophilia, Acinetobacter baumannii, and Proteus penneri were also identified in the NGS of 16S metagenomics. Understanding the bacterial microbiota that are native to the oropharynx of N. atra, in addition to the bite wound, may have additional therapeutic implications regarding empiric antibiotic selection for managing N. atra bites.
Topics: Adult; Aged; Animals; Anti-Bacterial Agents; Bacteria; Female; High-Throughput Nucleotide Sequencing; Humans; Male; Metagenomics; Middle Aged; Naja naja; Oropharynx; RNA, Ribosomal, 16S; Snake Bites; Taiwan; Wound Infection
PubMed: 33857127
DOI: 10.1371/journal.pntd.0009331 -
Cirugia Pediatrica : Organo Oficial de... Jan 2021Caustic burns still cause complex esophageal lesions in the pediatric population. However, therapeutic possibilities in severe cases are limited. A surgical approach...
INTRODUCTION
Caustic burns still cause complex esophageal lesions in the pediatric population. However, therapeutic possibilities in severe cases are limited. A surgical approach allowing for a longer neoesophagus, an isoperistaltic esophagus, and a better vascularization, with a lower risk of complications such as necrosis, stenosis, or perforation, is proposed.
CLINICAL CASE
16-month-old patient who accidentally ingested caustic soda. This caused a IIIb degree burn compromising the pharynx down to the stomach. Esophageal replacement with an isoperistaltic gastric tube was carried out, which allowed for a neoesophagus of appropriate length, an optimal vascularization for the graft, and physiological peristalsis.
COMMENTS
The surgical approach proposed allows the esophagus to be irrigated from the right gastro-omental artery, thus preserving irrigation of the greater curvature. It also allows for a longer esophagus, and thanks to anatomical positioning, for physiological peristalsis.
Topics: Burns, Chemical; Caustics; Child; Esophageal Stenosis; Humans; Infant; Stomach
PubMed: 33507643
DOI: No ID Found -
Medicine Nov 2020Hyperthyroidism-related anterior circulation ischemic events have been well documented; however, posterior circulation infarction is rarely reported, not to mention with...
An extensive posterior circulation infarction secondary to primary hyperthyroidism accompanied with superior mesenteric artery syndrome: A case report and description of patho-physiological association.
INTRODUCTION
Hyperthyroidism-related anterior circulation ischemic events have been well documented; however, posterior circulation infarction is rarely reported, not to mention with superior mesenteric artery syndrome (SMAS), which has never been reported concurrently. We describe, to the best of our knowledge, the first case of hyperthyroidism-related cerebellar infarction accompanied with SMAS.
PATIENT CONCERNS
A 22-year-old women presented with palpitation, postprandial vomiting, and acute body weight loss. Enlarged thyroid gland was discovered in physical examination and Graves disease was diagnosed by blood test; therefore, Propylthiouracil and β-blocker were prescribed. Sudden onset conscious disturbance accompanied with apnea was noted during hospitalization.
DIAGNOSIS
Computed tomography (CT) revealed cerebellar infarction with severe cerebellar swelling and tonsil herniation; hence, emergent suboccipital craniotomy and bilateral tonsillectomy were performed.
INTERVENTIONS
Nevertheless, persisted poor passage of liquid diet during nasogastric tube feeding was noted after operation. CT of abdomen showed a sharp aorta-SMA angle (15°) and a short distance between aorta and SMA (6 mm) indicating a diagnosis of SMAS.
OUTCOMES
After parental nutrition supplement and progressive rehabilitation program, she recovered to a modified Rankin Scale of 3.
CONCLUSION
Although rarely reported, hyperthyroidism-related sympathetic hyperstimulation, vasculopathy could result in potentially deadly posterior circulation infarction. Furthermore, SMAS should be considered in the cases of hyperthyroidism with prolonged gastrointestinal symptoms even after treatment and should be treated simultaneously, since SMAS exacerbates depletion of intravascular volume. Further study to clarify the relation between hyperthyroidism and posterior circulation hemodynamic status is suggested.
Topics: Chest Pain; Craniotomy; Female; Humans; Hyperparathyroidism, Primary; Infarction; Palatine Tonsil; Paralysis; Superior Mesenteric Artery Syndrome; Tomography, X-Ray Computed; Vomiting; Young Adult
PubMed: 33181647
DOI: 10.1097/MD.0000000000022664 -
International Journal of Surgery Case... 2020Pedicled flap reconstruction still plays an essential role in head and neck surgery as an alternative to free grafts. Two standard methods are the pectoralis major and...
INTRODUCTION
Pedicled flap reconstruction still plays an essential role in head and neck surgery as an alternative to free grafts. Two standard methods are the pectoralis major and the deltopectoral flap, which are generally characterized by their reliable perfusion. This case describes bilateral arteriosclerosis of the subclavian artery as a possible cause of flap failure.
PRESENTATION OF CASE
We report on a 65-year-old patient with a multilevel carcinoma of the right pharynx. Due to the unique patient history, a free flap reconstruction was not possible. After resection of the primary, we performed reconstruction with a pedicled pectoralis major flap.
DISCUSSION
Postoperatively, we observed necrosis of the pectoralis major flap. Secondary defect reconstructions were performed with a deltopectoral flap first from the right and then, in the case of necrosis, from the left side. Stenosing arteriosclerotic plaques of the subclavian artery on both sides were the cause of flap failure.
CONCLUSION
Preoperative angiography of the subclavian artery is not a standard diagnostic procedure in the surgical planning of pedicled flap reconstruction in the head and neck region. In exceptional cases, we recommend angiographic imaging of the supplying vessels to make a more precise flap selection and avoid complications.
PubMed: 33086164
DOI: 10.1016/j.ijscr.2020.10.030 -
Journal of Stroke and Cerebrovascular... Sep 2020Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this scenario, managing...
Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this scenario, managing acute medical conditions, such as stroke, requires a timely treatment together with proper strategies that minimize the risk of infection spreading to health care workers and other patients. We report the case of a 79-year-old woman, who was admitted for a wake-up stroke due to occlusion of the left middle cerebral artery. She was treated outside the COVID-19-dedicated track of the hospital because she had no concomitant signs or symptoms suggestive of SARS-CoV-2 infection nor recent contact with other infected individuals. Post-mortem nasal and pharyngeal swab was positive for SARS-CoV-2 infection. We propose that hyperacute stroke patients should be tested for SARS-CoV-2 infection at admission and then managed as having COVID-19 until cleared by a negative result. We are aware that such measure results in some delay of the acute treatment of stroke, which could be minimal using well-exercised containment protocols.
Topics: Aged; Betacoronavirus; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus Infections; Delayed Diagnosis; Fatal Outcome; Female; Humans; Infarction, Middle Cerebral Artery; Infectious Disease Transmission, Patient-to-Professional; Nose; Occupational Exposure; Pandemics; Pharynx; Pneumonia, Viral; Predictive Value of Tests; Risk Factors; SARS-CoV-2; Severity of Illness Index
PubMed: 32807416
DOI: 10.1016/j.jstrokecerebrovasdis.2020.104981